1. Field of the Invention
Various types of protein mediators (lymphokines) are produced when lymphocytes and monocytes undergo blast transformation from stimulation by, for instance, antigens, antibodies against surface components of the lymphocyte or certain plant mitogens. Two such lymphokines, Interleukin 1 (IL-1) and Interleukin 2 (IL-2), are known to modulate T and B cell immune responses in mammals, including: (1) enhancement of thymocyte mitrogensis; (2) induction of alloantigen specific cytotoxic T cell reactivity; and (3) assistance in the generation of helper T cells in antibody responses following stimulation with heterologous erythrocytes. In addition, IL-2 is capable both of sustaining the in vitro exponential proliferation of effector T cells lines and of inducing in vitro and vivo generation of cytotoxic T cells from nude mouse spleens.
Lymphokines like IL-1 are of multicellular origin, and through their multifaceted regulatory actions they affect a variety of different target cells during host response to infections. IL-1 at the site of inflammation activates lymphocytes, granulocytes, and fibroblasts. Moreover, IL-1 also may act as mediator of the acute-phase response, promote catabolism of structural protein and matrix and regulate the febrile response. To further elucidate these multiple biological effects on different tissues and to investigate whether they are regulated by a single family of related molecules, it is necessary to analyze the sequence of the IL-1 molecule and to develope antibodies directed against IL-1.
Two proteins that share human Interleukin-1(IL-1) activity but are structurally distinct molecules have been identified. These proteins, termed IL-1.alpha. and IL-1.beta., compete with one another for binding to IL-1 receptors and mediate similar biological activities. Both molecules are synthesized as large precursors (M.sub.r s.sup..about. 30,000) that are processed to smaller biologically active forms (M.sub.r s.sup..about. 17,500). However, they are encoded by two distinct complementary DNAs, show only a 26% amino acid homology, and have pI's (isoelectric pH's) of 5 and 7, respectively.
2. Description of the Related Art
The characterization of a monoclonal antibody directed against the biologically active site of human Interleukin-1 is discussed by Kock et al (1986) J. Exp. Med., 163: 463-468. A hybridoma antibody which inhibits Interleukin 2 activity is disclosed in U.S. Pat. Nos. 4,411,993 and 4,473,493. A process for making human antibody producing B-lymphocytes in described in U.S. Pat. No. 4,444,887. The cloning, sequence, and expression of two distinct human Interleukin-1 complimentary DNAs is discussed by March et al. (1985) Nature, 315: 641-647.